Sodium borohydride → 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-hydroxymethyl-pyrazin-2-yl)-propionamide

HRID 719903Notes

Reaction equation

HRID 719903 reaction equation
C[O:2][C:3]([C:5]1[CH:10]=[N:9][C:8]([NH:11][C:12](=[O:31])[C@@H:13]([C:20]2[CH:25]=[CH:24][C:23]([S:26]([CH3:29])(=[O:28])=[O:27])=[C:22]([Cl:30])[CH:21]=2)[CH2:14][CH:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:7][N:6]=1)=O.[BH4-].[Na+]>CO>[Cl:30][C:22]1[CH:21]=[C:20]([C@@H:13]([CH2:14][CH:15]2[CH2:16][CH2:17][CH2:18][CH2:19]2)[C:12]([NH:11][C:8]2[CH:7]=[N:6][C:5]([CH2:3][OH:2])=[CH:10][N:9]=2)=[O:31])[CH:25]=[CH:24][C:23]=1[S:26]([CH3:29])(=[O:27])=[O:28]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 674828615-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazine-2-carboxylic acid methyl ester

Product 1

HCID 674828462(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-hydroxymethyl-pyrazin-2-yl)-propionamideYield 59%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A suspension of 5-[2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-propionylamino]-pyrazine-2-carboxylic acid methyl ester (200 mg, 0.43 mmol) in methanol (2 mL) was cooled to 0° C. and then was treated with sodium borohydride (49.2 mg, 1.29 mmol). The reaction mixture was stirred at 0° C. for 5 min and then at 25° C. for 1.5 h. The reaction was cooled to 0° C. and then quenched with water. The reaction mixture was then diluted with ethyl acetate (75 mL), washed with a 1N aqueous hydrochloric acid solution (3×75 mL) and a saturated aqueous sodium chloride solution (75 mL), dried over sodium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 3/2 ethyl acetate/hexanes) afforded 2(R)-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl-N-(5-hydroxymethyl-pyrazin-2-yl)-propionamide (110.4 mg, 59%) as a white foam: mp 78–81° C. (foam to gel); (ES)+-HRMS m/e calcd for C20H24ClN3O4S (M+H)+ 438.1249, found 438.1252.

Workup

  1. waitat 25° C. for 1.5 h
  2. temperatureThe reaction was cooled to 0° C.
  3. customquenched with water
  4. additionThe reaction mixture was then diluted with ethyl acetate (75 mL)
  5. washwashed with a 1N aqueous hydrochloric acid solution (3×75 mL)
  6. dry with materiala saturated aqueous sodium chloride solution (75 mL), dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0a8d4104c22b4778af71dcccabc4ac84
Source dataset
uspto-grants-2006_11
Patent number
US07132425B2

Reaction notes

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